Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular zone in the hypothalamus.

Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular zone in the hypothalamus.
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下丘脑室旁核和室旁下区的超电钙节律

DOI:
10.1073/pnas.1804300115
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发表时间:
2018-10-02
影响因子:
11.1
通讯作者:
Honma S
Honma S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wu YE;Enoki R;Oda Y;Huang ZL;Honma KI;Honma S

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尽管哺乳动物的各种功能以超常的方式波动,但节律的起源和机制在很大程度上是未知的。在这项研究中,我们发现了下丘脑室旁核(PVN)、室旁带(SPZ)和视交叉上核(SCN)的同步超昼夜钙节律。超昼夜节律起源于SPZ-PVN区并传递到SCN。神经化学干预表明,谷氨酸能机制对超昼夜节律的产生和河豚毒素敏感神经网络的同步至关重要。gaba能系统可能在改善昼夜节律输出信号方面发挥作用。该研究为了解下丘脑超昼夜节律的位点和机制提供了第一个线索。哺乳动物的主生物钟视交叉上核(SCN)向室旁亚区(SPZ)和室旁核(PVN)发送主要的输出信号,其神经机制在很大程度上是未知的。在本研究中,连续测量了含有PVN、SPZ和SCN的下丘脑培养切片的细胞内钙水平。我们在SPZ-PVN和SCN区域检测到周期为0.5-4.0小时的超昼夜钙节律,其频率取决于SPZ-PVN区域的局部昼夜节律。超昼夜节律在整个SPZ-PVN区和部分SCN区是同步的。由于在仅scn切片中未检测到超昼夜节律,因此超昼夜节律的起源是SPZ-PVN区域。细胞内钙以毫秒级的速度快速增加,其频率决定了超声心动图的振幅。钠离子通道阻滞剂河豚毒素使同步超昼夜节律去同步并抑制,表明河豚毒素敏感网络参与了同步超昼夜节律。相反,超昼夜节律被谷氨酸受体阻滞剂消除,表明谷氨酸能机制在超昼夜节律产生中起关键作用,而GABAA受体阻滞剂增加了超昼夜节律的频率并改变了SCN的昼夜节律。gaba能网络可以改善昼夜节律输出信号。本研究为揭示超昼夜节律的基因位点和网络机制提供了线索。
Significance Despite that the various functions in mammals fluctuate in the ultradian fashion, the origin and mechanism of the rhythm are largely unknown. In this study, we found synchronous ultradian calcium rhythms in the hypothalamic paraventricular nucleus (PVN), subparaventricular zone (SPZ), and suprachiasmatic nucleus (SCN). The ultradian rhythms were originated from the SPZ-PVN region and transmitted to the SCN. Neurochemical interventions revealed that the glutamatergic mechanism is critical for generation and a tetrodotoxin-sensitive neural network for synchrony of the ultradian rhythm. The GABAergic system could have a role in refining the circadian output signals. The study provides the first clue to understand the loci and mechanism of ultradian rhythm in the hypothalamus. The suprachiasmatic nucleus (SCN), the master circadian clock in mammals, sends major output signals to the subparaventricular zone (SPZ) and further to the paraventricular nucleus (PVN), the neural mechanism of which is largely unknown. In this study, the intracellular calcium levels were measured continuously in cultured hypothalamic slices containing the PVN, SPZ, and SCN. We detected ultradian calcium rhythms in both the SPZ-PVN and SCN regions with periods of 0.5–4.0 hours, the frequency of which depended on the local circadian rhythm in the SPZ-PVN region. The ultradian rhythms were synchronous in the entire SPZ-PVN region and a part of the SCN. Because the ultradian rhythms were not detected in the SCN-only slice, the origin of ultradian rhythm is the SPZ-PVN region. In association with an ultradian bout, a rapid increase of intracellular calcium in a millisecond order was detected, the frequency of which determined the amplitude of an ultradian bout. The synchronous ultradian rhythms were desynchronized and depressed by a sodium channel blocker tetrodotoxin, suggesting that a tetrodotoxin-sensitive network is involved in synchrony of the ultradian bouts. In contrast, the ultradian rhythm is abolished by glutamate receptor blockers, indicating the critical role of glutamatergic mechanism in ultradian rhythm generation, while a GABAA receptor blocker increased the frequency of ultradian rhythm and modified the circadian rhythm in the SCN. A GABAergic network may refine the circadian output signals. The present study provides a clue to unraveling the loci and network mechanisms of the ultradian rhythm.
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发表时间: 2017-02-03
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影响因子: 4.6
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影响因子: 11.1
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